Oral Misoprostol alone versus oral misoprostol followed by oxytocin for labour induction in women with hypertension in pregnancy (MOLI): protocol for a randomised controlled trial

Hillary Bracken,Andrew Weeks,Beverly Winikoff,Mark Turner,Zarko Alfirevic,Shuchita Mundle,Kate Lightly,Simon Leigh,Thomas Easterling,Robbie Kerr,Brian Faragher

doi:10.1186/s12884-021-04009-8

Abstract

BackgroundEvery year approximately 30,000 women die from hypertensive disease in pregnancy. Magnesium sulphate and anti-hypertensives reduce morbidity, but delivery is the only cure. Low dose oral misoprostol, a prostaglandin E1 analogue, is a highly effective method for labour induction. Usually, once active labour has commenced, the misoprostol is replaced with an intravenous oxytocin infusion if ongoing stimulation is required. However, some studies have shown that oral misoprostol can be continued into active labour, a simpler and potentially more acceptable protocol for women. To date, these two protocols have never been directly compared.MethodsThis pragmatic, open-label, randomised trial will compare a misoprostol alone labour induction protocol with the standard misoprostol plus oxytocin protocol in three Indian hospitals. The study will recruit 520 pregnant women being induced for hypertensive disease in pregnancy and requiring augmentation after membrane rupture. Participants will be randomised to receive either further oral misoprostol 25mcg every 2 h, or titrated intravenous oxytocin. The primary outcome will be caesarean birth. Secondary outcomes will assess the efficacy of the induction process, maternal and fetal/neonatal complications and patient acceptability. This protocol (version 1.04) adheres to the SPIRIT checklist. A cost-effectiveness analysis, situational analysis and formal qualitative assessment of women’s experience are also planned.DiscussionAvoiding oxytocin and continuing low dose misoprostol into active labour may have a number of benefits for both women and the health care system. Misoprostol is heat stable, oral medication and thus easy to store, transport and administer; qualities particularly desirable in low resource settings. An oral medication protocol requires less equipment (e.g. electronic infusion pumps) and may free up health care providers to assist with other aspects of the woman’s care. The simplicity of the protocol may also help to reduce human errors associated with the delivery of intravenous infusions. Finally, women may prefer to be mobile during labour and not restricted by an intravenous infusion. There is a need, therefore, to assess whether augmentation using oral misoprostol is superior clinically and economically to the standard protocol of intravenous oxytocin.Trial registrationClinical Trials.gov, NCT03749902, registered on 21st Nov 2018.

Highlights

Every year approximately 30,000 women die from hypertensive disease in pregnancy
Hypertensive disease in pregnancy is a major cause of the 300,000 maternal deaths that occur every year [1]
The Cochrane review concluded that “low-dose oral misoprostol probably has many benefits over other methods for labour induction.” and that “a starting dose of 25 μg may offer a good balance of efficacy and safety.”

Summary

Introduction

Every year approximately 30,000 women die from hypertensive disease in pregnancy. Magnesium sulphate and anti-hypertensives reduce morbidity, but delivery is the only cure. A prostaglandin E1 analogue, is a highly effective method for labour induction. Some studies have shown that oral misoprostol can be continued into active labour, a simpler and potentially more acceptable protocol for women. To date, these two protocols have never been directly compared. In South Asia alone, hypertensive disease in pregnancy is responsible for 10,000 deaths annually [2] Much of this burden could be prevented by timely and effective delivery—the only curative intervention in pre-eclampsia. Misoprostol, a prostaglandin E1 analogue, given in low doses orally is a highly effective method for labour induction in low resource settings. The Cochrane review concluded that “low-dose oral misoprostol probably has many benefits over other methods for labour induction.” and that “a starting dose of 25 μg may offer a good balance of efficacy and safety.” A recent network meta-analysis of all prostaglandins for labour induction supported these conclusions, finding that oral misoprostol solution (< 50mcg) was the safest in terms of risk of caesarean section [5]

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